1. Non-Neoplastic Pancreas
Benjamin Swanson, MD, PhD
Assistant Professor, Department of Pathology
Hello, I’m Ben Swanson, and I’ll be reviewing non-neoplastic pancreatic pathology.
Biographic information
Title, Department Information
Clinical Interest
Research Interest

2. Learning Objectives
Define pancreas divisum, explain its embryologic origin and clinical manifestations.
Define annular pancreas, its clinical presentation and embryologic origin.
Describe the conditions, etiologic agents, clinical manifestations, and complications associated with acute and chronic pancreatitis.
Understand the underlying pathophysiology resulting in the global manifestations of acute pancreatitis.
At the conclusion of the lecture, I would like you to
Be able to define pancreatic divisum, explaining its embryologic origin and clinical manifestatations
Define annular pancreas, its clinical presentation and embryologic origin
Describe the conditions, etiologic agents, clinical manifestations, and complications associated with acute and chronic pancreatitis
And understand the underlying pathophysiology resulting in the global manifestations of acute pancreatitis

3. Congenital Anomalies Agenesis, hypoplasia Annular Pancreas divisum
Aberrant pancreas (ectopic)
Duct anomalies
Congenital anomalies of the pancreas include agenesis, hypoplasia, annular pancreas, pancreatic divisum, aberrant pancreas (ectopic), and duct anomalies.

4. Annular Pancreas Pancreas arises from dorsal and ventral duodenal buds
In the 6th week of normal pancreas development, the ventral pancreas with the common bile duct, rotates around the posterior duodenum
In annular pancreas, a portion of the ventral primordium becomes fixed to the duodenum while the other portion rotates around the duodenum
Embryologically, the pancreas arises from dorsal and ventral duodenal buds. In the sixth week of development, the ventral pancreas and the common bile duct rotate circumferentially around the duodenum. Annular pancreas, which you can see in the blue box, represents a ring of pancreas encircling the duodenum. It is hypothesized to develop due to the failure of one of the lobes of the ventral duodenal bud to regress (the ventral primordium becomes fixed to the duodenum). The other portion of primordial pancreas rotates around the pancreas.
Pancreas

5. Annular Pancreas
This remnant forms a band-like ring around the the second portion of the duodendum
Can present as duodenal obstruction with gastric distension and vomiting
This remnant forms a band-like ring around the second portion of the duodenum. This rare condition, accounting for 0.015% of the population, can cause duodenal obstruction, gastric distension and vomiting.

6. Pancreas Divisum
Most common congenital anomaly of the pancreas (5-10% of population)
Caused by an anomaly in the fusion of the duct systems of the primordial ventral and dorsal pancreas
In complete divisum, the larger portion of the pancreas drains through the minor papilla stenosis may predispose to pancreatitis
Pancreas divisum is the most common congenital anomaly of the pancreas, seen in 5-10% of the population. It is due to lack of fusion of the two duodenal (ventral and dorsal) embryologic buds. It can be complete, as seen in the first image on the left, where we have a complete separation of between the pancreatic head and the pancreatic body and tail. This causes the larger portion of pancreas to drain through the minor papilla. This can lead to stenosis and may predispose to pancreatitis.
Alternatively, pancreatic divisum can be partial, as seen on the image on the right where there is some degree of fusion of the two buds, but there is an abnormal anatomy.
Complete
Partial

7. Acute Pancreatitis Can occur at any age
Most commonly occurs in 3rd to 6th decade of life
Early presentation (1st decade of life)  hereditary, infection or trauma
Mild “edematous” pancreatitis
Minimal organ dysfunction
Uneventful recovery in 5-7 days
Severe “necrotizing” pancreatitis
Multisystem organ failure (Acute respiratory distress syndrome, Acute tubular necrosis of the kidney, Disseminated intravascular coagulation, Sepsis)
Abscess and pseudocyst formation
Duodenal obstruction
Mortality ~10%
Acute pancreatitis can occur at any age. It most commonly occurs in adults in the third to sixth decade of life. When it occurs in the first decade of life, this is suggestive of a hereditary cause, infection or trauma. In mild “edematous” pancreatitis there is minimal organ dysfunction with an uneventful recovery in 5-7 days. In contrast, severe “necrotizing” pancreatitis may present with multisystem organ failure (such as acute respiratory distress syndrome of the lungs, acute tubular necrosis of the kidneys, disseminated intrasvascular coagulation or sepsis), abscess formation in the pancreas. Furthermore, there can be duodenal obstruction and even mortality in approximately 10% of patients with severe pancreatitis.

8. Acute Pancreatitis Etiology
Alcohol
Gallstones
Metabolic disorders (hyperlipidemia, hypercalcemia)
Medications
Infections:
Viral: Mumps, coxsackie, hepatitis B, CMV, varicella-zoster, HSV, HIV
Bacteria: mycoplasma, Legionella, Leptospira, salmonella
Fungi: Aspergillus
Parasites: Toxoplasma, cryptosporidium, Ascaris
Trauma/post-procedural
Vascular/shock
Congenital: Pancreatic divisum
Genetic: Cystic Fibrosis, alpha-1 antitrypsin deficiency
Account for most cases (60-75%)
The most common cause of acute pancreatitis are gallstones and alcohol, accounting for 60-75% of patients. Other causes of acute pancreatitis include metabolic disorders such as hyperlipidemia and hypercalcemia, various medications, various infections, trauma, following a medical procedure involving the pancreas and in patients with shock. Genetic causes of acute pancreatitis include cystic fibrosis and alpha-1 antitrypsin deficiency.

9. Pathophysiology of Acute pancreatitis
Pathophysiologically, acute pancreatitis is a result of damage to the acini. Either directly or indirectly through bile reflux, this causes relase of oxygen free radicals and pancreatic enzymes which cause damage to the pancreas and surrounding tissues.

10. Acute Pancreatitis Macroscopic Findings
Mild acute pancreatitis
Swollen pale and indurated pancreas
Lobules appear separated by edema
Focal fat necrosis
Severe acute pancreatitis
Large confluent areas of fat necrosis
Hemorrhagic necrosis may develop
The anatomic findings in mild acute pancreatitis include a swollen, pale and indurated pancreas with lobules of the pancreas separated by edema. Grossly, fat necrosis appears as opaque white, waxy, or chalky areas. In severe acute pancreatitis, by contrast, has large confluent areas of fat necrosis that may or may not have hemorrhage.

11. Acute Pancreatitis Microscopic Findings
Mild acute pancreatitis
Interstitial acute inflammation
Spotty peripancreatic fat necrosis
Severe acute pancreatitis
Abundant neutrophils
Large areas of fat necrosis
Variable levels of pancreatic necrosis
Saponification
Microscopically, mild acute pancreatitis shows spotty peripancreatitc fat necrosis (as indicated by the black arrow)and interstitial acute inflammation. In severe acute pancreatitis, there can be large areas of fat necrosis and variable pancreatic parenchymal necrosis spread throughout. These cases will also show abundant neutrophils, saponification (as indicated by the white arrow), hemorrhage, and venous thrombosis.

12. Chronic Pancreatitis Incidence
Can occur at any age
Alcohol related chronic pancreatitis more commonly affects males >40 yo
Chronic pancreatitis in childhood represents hereditary etiologies
Chronic pancreatitis can occur at any age. Alcohol-related chronic pancreatitis usually affects adults greater than 40 years of age and is more common in men. Chronic pancreatitis presenting in childhood is usually due to hereditary or tropical etiologies.

13. Chronic Pancreatitis Etiology
Chronic alcohol ingestion
Most common cause in developed countries (70%)
Only 10% of alcohol abusers develop chronic pancreatitis which suggests additional factors account for its development
Concurrent smoking may multiple the risk of chronic pancreatititis with 10X
Duct obstruction: choledocholithiasis, tumors, scarring/stenosis
Groove pancreatitis (paraduodenal wall cyst)
Metabolic: hypercalcemia, hyperlipidemia
Alcohol ingestion is by far the common cause of chronic pancreatitis. Approximately 70% of chronic pancreatitis cases are caused by alcohol. However, only 10% of alcohol abusers develop chronic pancreatitis, which suggests that additional factors are at play. Importantly, smoking is an additive risk factor for developing chronic pancreatitis with alcohol, with perhaps a 10 fold greater risk of developing chronic pancreatitis. Duct obstruction is another potential cause of chronic pancreatitis. Choledocholithiasis, tumors, scarring and stenosis can all cause duct obstruction and lead to chronic pancreatitis. Metabolic causes include hypercalcemia and hyperlipidemia. Groove pancreatitis (also called paraduodenal wall cyst) can also chronic pancreatitis.

14. Chronic Pancreatitis Etiology
Tropical
Aggressive form of juvenile pancreatitis which occurs in tropical developing countries
May be related to malnutrition, toxins or genetic predisposition
Hereditary: PRSS1, CFTR, SPINK1
Trauma
Idiopathic: up to 25% of cases
Tropical chronic pancreatitis is an aggressive form of juvenile pancreatitis that occurs in tropical developing countries. It is theorized to be due to malnutrition, toxin exposure and/or genetic predisposition. Genetic syndromes and trauma can also cause chronic pancreatitis. Up to 25% of cases have no known cause.

15. Chronic Pancreatitis Macroscopic Findings
Pancreas may be involved focally, diffusely, or segmentally
Affected pancreas usually firm, indurated and fibrotic
Cystically dilated pancreatic ducts
Grossly, the pancreas in chronic pancreatitis is enlarged, firm, indurated and fibrotic. This can focally, segmentally, or diffusely involve the pancreas. Additionally, the pancreatic duct may be cystically dilated.

16. Chronic Pancreatitis Microscopic Findings
Preserved lobular arrangement of the pancreas
Duct and acinar atrophy leads to more prominent appearing islets of Langerhans
Pancreatic duct alterations
Atrophy (can be angulated)
Hyperplasia (pseudopapillary or papillary)
Metaplasia (squamous, mucinous, pyloric)
Fibrosis
Chronic inflammation
Microscopically, chronic pancreatitis shows preservation of the normal lobular architecture of the pancreas. This is important for distinguishing chronic pancreatitis from pancreatic cancer. Duct and acinar atrophy are seen in an irregular distribution throughout the pancreas. Pancreatic duct alterations include: atrophy (where they appear angulated.), hyperplasia (which can be pseudopapillary or papillary) and metaplasia. Chronic inflammation is often seen, but is not the predominant feature. Scattered fibrosis is often a seen. Although the islets of Langerhans are not involved, they appear relatively increased due to the acinar atrophy.

17. Chronic Pancreatitis Acinar Atrophy
This image demonstrates acinar atrophy. The white circle shows a preserved area of acini surrounding an islet of Langerhans. The black circle shows an area of fibrosis where only a small islet of Langerhans remains and the pancreatic acini have atrophied.

18. Chronic Pancreatitis Fibrosis and Chronic Inflammation
This image depicts the fibrosis and chronic inflammation in chronic pancreatitis. The white arrow shows chronic inflammation while the black arrow depicts fibrosis.

19. Chronic Pancreatitis Spared Islets
This image demonstrates the relative sparing of islets of Langerhans in chronic pancreatitis.

20. Pancreatic Pseudocyst
Occurs as a result of pancreatitis (acute or chronic)
Most commonly associated with alcohol consumption
Grossly is a unilocular cyst with a ragged inner surface and a thick fibrotic wall
Fluid within the cyst has few cells and has high levels of the enzyme amylase
Pancreatic pseudocyst occurs most commonly as a result of acute or chronic pancreatitis. They are most commonly associated with chronic alcohol consumption. Grossly, the pseudocyst consists of a unilocular cyst with a ragged inner surface and a thick fibrotic wall. The cyst fluid on fine needle aspiration has high levels of amylase and scant numbers of cells.

21. Pancreatic Pseudocyst
Microscopically lacks an epithelial lining (thus pseudocyst). Cyst wall lined by granulation tissue
Microscopically also lacks necrosis (as opposed to an abscess)
Microscopically, the pseudocyst lacks an epithelial lining. The lining of the wall has granulation tissue, inflammatory cells, and fibrosis. These pseudocysts lack necrosis, as compared to an abscess.

22. Summary
Pancreatic divisum is a complete or partial division of the pancreas, it is caused by lack of fusion of the two embryologic duodenal buds
Annular pancreas is an encircling of the duodenum by the pancreas, it is caused by failure of the ventral duodenal bud to properly rotate with the duodenum
Acute pancreatitis is most commonly caused by alcohol or gallstones; it microscopically shows acute inflammation and necrosis
Chronic pancreatitis microscopically shows fibrosis, acinar atrophy and chronic inflammation
In summary, pancreas divisum is due to the lack of fusion of the two embryologic duodenal buds. It may be complete or partial. Annular pancreas is an encircling of the duodenum by the pancreas that is due to the failure of one of the embryologic buds to properly rotate with the duodenum. Acute pancreatitis commonly occurs with gallstone and ethanol abuse. Acute pancreatitis shows acute inflammation and necrosis. Chronic pancreatitis shows chronic inflammation, fibrosis and acinar atrophy microscopically.

23. Non neoplastic pancreas quiz

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